It has been known for 30 years that human plasma has the ability to diminish the pyrogenicity of endotoxins derived from the Gram-negative bacteria. Numerous studies have since been reported in the literature demonstrating that plasma contains an endotoxin-inactivator which reacts with the lipid moiety of lipopolysaccharides of endotoxins thus rendering those toxins no longer pyrogenic. In plasma fractionation industry, manufacturers often find their final clinical plasma products, such as albumin, immune globulins, antihemophilic factor and others being pyrogenic thus resulting in the loss of the entire lot which is no longer suitable for intravenous injection. The monetary loss each year due to pyrogenic products must have been in the hundreds of thousands, if not millions of dollars. A large scale method has been developed to depyrogenate clinical albumin by this principal investigator. It consists of mixing plasma with pyrogenic albumin followed by a precipitation step to remove all plasma proteins including the inactivator and endotoxins, leaving only albumin in the supernatant. This method has been included in the amendment of the albumin license of the New York Blood Center. However, it is obvious that this method cannot be used for depyrogenation of other clinical plasma products due to different purification steps involved. The proposed research is to develop a large scale method for isolation of this inactivator by affinity adsorption from large plasma pools prior to plasma fractionation by ethanol so that it can be added to any pyrogenic plasma products without adversely affecting their purity or their safety. The inactivator-depleted plasma could still be used for routine plasma fractionation. Attempts will also be made to insolubilize the inactivator on a matrix (e.g., Sepharose) so that any pyrogenic parenterals intended for injection can be made non-pyrogenic by mixing with EI-Sepharose followed by filtration.